September 09, 2004
Reliability Theory Applied To Human Aging
Dr. Leonid A. Gavrilov and Dr. Natalia S. Gavrilova have a new article out in the IEEE Spectrum on their reliability engineering approach to understanding aging.
If only we could maintain our body functions as they are at age 10, we could expect to live about 5000 years on average. Unfortunately, from age 11 on, it's all downhill!
The problem is that our bodies deteriorate with age. For most of our lives, the risk of death is increasing exponentially, doubling every eight years. So, why do we fall apart, and what can we do about it?
They go on to explain how engineering reliability theory can be applied to understanding how humans age and die. One of their conclusions is the same position argued for by rejuvenation advocates: we need to develop the ability to grow replacement parts and to do more kinds of repairs.
Their point that we start increasing our risk of dying of aging from about age 11 is demonstrated by a recent study led by Dr Faisal Khan of the University of Dundee in the UK. Dundee and colleagues found that children as young as 11 years old already show signs of endothelial cell dysfunction that will contribute to the development of heart disease and other circulatory diseases.
“This is the stage of life where changes to a person’s body are potentially reversible,” says lead researcher Faisal Khan at the University of Dundee, UK. “If you leave it until their 30s or 40s, it is much harder.”
Khan and his colleagues studied the lining of tiny blood vessels, or endothelium, in 158 Scottish children, aged 11 to 14. Within this group, 20% of children showed impaired endothelial activity.
In some children capillaries failed to expand in response to drug exposure.
The researchers rubbed a drug through their skin to make their blood vessels expand. The vessels were then monitored using a laser.
In about 20 per cent of children, the tiny capillaries and arteries failed to expand, suggesting that the cells lining the vessels, a layer called the endothelium, was damaged. Endothelial cells control a vessel's ability to contract and dilate.
Poorly performing epithelial cells will eventually lead to bigger problems.
Problems in the cells that make up endothelium can lead to progressive hardening and narrowing of blood vessels, called atherosclerosis, which can ultimately lead to cardiovascular diseases.
The rate of malfunction of epithelial cells is higher in obese kids. Even in youth bad diets begin the process of accumulation of aging damage. It is never too soon to start eating a healthful diet.
How many defects we are born with determines how much redundancy we have to start out with in all our bodiy systems. We all start out with a different total number of microscopic errors in our bodies at birth. From that point on the rates at which we accumulate more damage varies from person to person and under different living conditions. There is some amount of randomness as to where the damage occurs.
We are actually better off if the damage accumulation is more evenly spread. If the damage accumulation is concentrated in a sinlge essential component then that component will fail sooner and kill us sooner.
We need better ways to slow damage accumulation. But even more so we need techniques for doing repair and replacement. Cell therapy, growth of replacement organs, and techniques for getting rid of accumulated junk are just a few of the several Strategies of Engineered Negligible Senescence that could fix our accumulated damage and restore redundancy to our aging body parts.
Part of the problem is that we are not designed for easy maintenance. If I need a new heart, just opening up my chest is a big deal. Then there are various compatibility issues with any other human heart (probably selected for to make the spread of disease through similar hosts harder). Then the replacement itself - like trying to change an engine in a car that would experience irreversible brain death if it ever stopped running for more than a few minutes. Then you have to recover.
Babies should be born with modular design, and a little incubator with replacement parts. Also a warranty.
I agree we are not designed for field upgrades and repairs. The heart is an extreme case because stopping it even for short periods probably causes some amount of brain damage under the best of conditions. Though likely we will make progress in the development of methods for heart replacement that cause less damage in the rest of the body.
Stem cell therapies will eventually allow repair of hearts by replacement of cells rather than replacement of the whole organ. Ditto for cell therapy aimed at other organs as well as rejuvenating gene therapy aimed at cells in organs.
We will also eventuall develop techniques for making cells grow old less rapidly. For instance, move the mitochondrial DNA into the nucleus. Also, develop variations on a variety of enzymes that cause them to make errors less rapidly. Enzymes that more accurately replicate and repair DNA would be great.
The development of better longer-lasting parts will Increase in Mean Time Between Failures (MTBF) and reduce the need for surgeries to put in new body parts. I'm looking forward to getting organs with MTBFs measured in the hundreds of years.
David: “Part of the problem is that we are not designed for easy maintenance.”
I believe we may indeed be designed for easy maintenance. The stem cells in our bone marrow should provide a renewable supply of new stem cells that travel through the blood to injury sites. Unfortunately not all damage is healed before the wound stops attracting stem cells. And as we age the repair process doesn’t work nearly as well. (As we get older we have fewer circulating stem cells in our blood.)
I think there is a good chance that once we understand what attracts stem cells to damaged areas and once we understand what triggers stem cell production in the bone marrow that therapies will be developed so that regeneration is significantly enhanced.
Sorry to be off topic, Randall. But I want to share my view on blondes with you (I can't find a way to email you). Here's my take.
Blondes are in short supply nowadays if we look at the overall population trends worldwide. I think someone should start a business to "produce" more blondes. Here's the idea. Collect and store sperm from attractive blond men. Then, enlist attractive blonde women to be egg donors. The blond sperm will be matched with the blonde eggs to form blonde embryos. Now, here comes the critical part, the frozen embryos will be made available to non-blondes or even non-Caucasian women. For example, an Asian woman can choose to give birth to a blonde child and raise the child as her own this way. Even better yet, the sex of the embryo can be pre-selected by sorting the X and Y chromosome sperm before fertilization.
If I had my way, I would start this business and encourage women of all ethnicities to choose a blonde daughter. Think of the effect on the world, especially the Third World. The mess that is happening and worsening day by day will slowly be transformed with the injection of blonde beauties.
Let's admit it. Blondes are more fun and blondes have more fun. Men all over the world prefer blondes (generally speaking). So, if men all over the world have blondes to love, then there wouldn't be so much fighting and bloodshed. People would be busy loving and romancing each other. Better yet, if more and more blond men are created, then the overall picture of the entire world will become more "golden." When more people start to love themselves and love each other, more good energy is generated. The world will become less violent. There will be more hope, more happiness, more harmony, and more goodwill.
To wrap up, let me predict the future of the world in two words: blonde paradise. (Which will take at least two centuries, I guess.... and hope....)
This is an attempt to return a discussion back to its original topic by posting a relevant Press Release for this new article:
Newswise (press release) - Aug 26, 2004
Why We Fall Apart
Engineering's reliability theory explains human aging.
Newswise — The quest to understand and control aging has led University of Chicago biologists Leonid Gavrilov and Natalia Gavrilova to draw inspiration from what might seem an unlikely source: reliability engineering. The reliability-engineering approach to understanding aging is based on ideas, methods, and models borrowed from reliability theory. Developed in the late 1950s to describe the failure and aging of complex electrical and electronic equipment, reliability theory has been greatly improved over the last several decades. It allows researchers to predict how a system with a specified architecture and level of reliability of the constituent parts will fail over time. But the theory is so general in scope that it can be applied to understanding aging in living organisms as well. In the ways that we age and die, Gavrilov and Gavrilova find, we are not so different from the machines we build. "The difference is minimized if we think of ourselves in this unflattering way: we are like machines made up of redundant components, many of which are defective right from the start," the two write in the September issue of IEEE Spectrum.
In reliability theory, aging is defined through the increased risk of failure. More precisely, something ages if it is more likely to fall apart, or die, tomorrow than today. If the risk of failure does not increase as time passes, then there is no aging. By looking closely at human aging data, the University of Chicago researchers noted striking similarities between how living organisms and technical devices age and fail. In both cases, the failure rate follows a curve shaped roughly like a bathtub. The curve consists of three stages, called infant mortality, normal working, and aging. Death rates are rather high during infant mortality, but then drop to a low constant rate during the normal-working period. In humans, "this period is all too short, just 10 to 15 years, starting at about age 5," write Gavrilov and Gavrilova, a husband and wife team. "If only we could maintain our body functions as they are at age 10, we could expect to live about 5000 years on average."
Machines and humans even share these strange characteristics at very old age. As humans approach the age of 100, the risk of death stops increasing exponentially and instead begins to plateau. "If you live to be 110, your chances of seeing your next birthday are not very good, but, paradoxically, they are not much worse than they were when you were 102," the authors write. "There have been a number of attempts to explain the biology behind this in terms of reproduction and evolution, but since the same phenomenon is found not only in humans, but also in such man-made stuff as steel, industrial relays, and the thermal insulation of motors, reliability theory may offer a better way."
An immediate consequence of the last observation is that there is no fixed upper limit to human longevity--there is no special number that separates possible from impossible values of a life span. This conclusion flies in the face of the common belief in the existence of a fixed maximal human life span and a biological limit to longevity. The University of Chicago researchers were able to adapt reliability theory to biological aging by thinking of humans as a collection of redundant parts that do not, in themselves, age. But to get the model to work exactly, Gavrilov and Gavrilova had to make a radical assumption. Instead of humans starting life in pristine condition, the reliability equations suggest that we actually start with a great many defective parts. "If we accept the idea that we are born with a large amount of damage, it follows that even small improvements to the processes of early human development--ones that increase the numbers of initially functional elements--could result in a remarkable fall in mortality and a significant extension of human life," write Gavrilov and Gavrilova.
I'm trying to figure out how your theory can be practically applied. One possible direction to go with it is to measure different levels of redundancy in different people at young ages to tell them what particular parts of their bodies they need to try hardest to protect from damage.
How hard do you think it will turn out to be to measure how much redundancy each person has in various organs and other bodily subsystems while still at a fairly young age? I'm struck by how capillary health could be examined in children to look for early signs of decay.
Are there particular organs that will be easier to measure for redundancy? One problem I see is fhat if, say, a kidney has enough redundancy by a factor of 10 it may act the same as a kidney that has enough redundancy by a factor of 5. We'd need some non-life threatening way to put a load on an organ or to otherwise get it to act in a way that allows its amount of excess capacity to be measured.
One problem with life extending therapies is that they take a long time to test. If the therapeutic end-point is actual total months and years lived then it takes too long to test any therapy. Can your theory provide some sort of way to organize attempts to judge the usefulness of various aging biomarkers to detect much more quickly whether a given therapy aimed at slowing or reversing aging is really going to raise average life expectancy?
Also, can mathematical simulation models of biological systems be used to test whether various biomarkers are accurate predictors of life expectancy? Could, for instance, a model of various organs with reduced redundancy in the organs show which types of stresses (e.g. heat, cold, various types of infections, lack of sleep, etc) would most likely precipitate a life-threatening medical crisis?